ASP Scan (Weekly) for Apr 20, 2018

More super-resistant gonorrhea
Penicillin 'allergy' and prescribing
Candida auris in Colombia
New colistin resistance gene
More MCR-1 in China
E coli in Iranian dairy products
Colistin stewardship in South Africa
Artificial antimicrobial peptide

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

Good news about UK 'super gonorrhea' case—but 2 new infections noted

UK officials today report good news on the outcome of the man treated for a highly resistant Neisseria gonorrhoeae infection, but they also note two similar cases in Australia.

In an update from Public Health England (PHE), Gwenda Hughes, PhD, head of the agency's Sexually Transmitted Infection Section, said, "We are pleased to report that the case of multi-drug resistant gonorrhoea has been successfully treated. Investigations have also revealed there has been no further spread of this infection within the UK. PHE continues to actively monitor and tackle the spread of antibiotic resistance in gonorrhoea and potential treatment failures."

The man had contracted gonorrhea after having sex with a woman in Southeast Asia. PHE first reported his case on Mar 28. In a full report on the case today, PHE experts said, "Efforts to contact the partner in south east Asia are ongoing."

Hughes said of the Australian infections, "Two similar cases have just been reported in Australia and serve as a timely reminder that we expect to see further cases of multi-drug resistant gonorrhoea in the future. These cases will be challenging for healthcare professionals to manage."

The full report added, "Two cases of gonorrhoea with resistance to ceftriaxone, azithromycin, ciprofloxacin, penicillin, and tetracycline have subsequently been reported in Australia: one had had sex recently in south east Asia; the other case had no recent overseas travel."
Apr 20 PHE update
Apr 20 full PHE report
Mar 28 CIDRAP News story on the UK case


Removing penicillin allergy label from kids saves antibiotics, money

A study today by US researchers reveals that children with low-risk penicillin allergy symptoms whose test results were negative for penicillin allergy tolerated a penicillin challenge without a severe allergic reaction, and the cost savings of removing the penicillin allergy label from these patients was substantial.

As detailed in Pediatrics, the investigators had previously performed three-tier penicillin allergy testing on children with low-risk symptoms, and all of them tolerated a penicillin challenge without an allergic reaction. They hypothesized that the children would have no serious allergic reactions after re-exposure to penicillin.

In the new study, the researchers conducted a case series on 100 children whose tests were negative for penicillin allergy. In the year after they were tested for penicillin allergy, 36 of the kids received a total of 46 prescriptions, 26 of which (58%) were for penicillin derivatives. None of these children had an adverse reaction; 1 developed a rash.

The team determined that "delabeling" the children as no longer penicillin allergic saved $1,368 per patient, with an additional cost avoidance of $1,812, for a potential total cost saving for the pediatric emergency department of $192,223.

The authors conclude, "Delabeling children changed prescription behavior and led to actual health care savings."
Apr 20 Pediatrics abstract


Colombia reports 123 recent Candida auris cases

A report today in Morbidity and Mortality Weekly Report (MMWR) details 123 newly identified Candida auris infections in Colombia, noting that the pathogen has been present there since at least 2015 and that case counts are increasing.

After the US Centers for Disease Control and Prevention issued an alert in 2016 about the worrisome fungal infection, Colombian scientists re-investigated 45 isolates from 2013 through 2016 that had been classified as C haemolunii, which is often misidentified. Upon retesting, all of them proved to be C auris, with the most recent being from 2015, and Colombian officials released a clinical alert for heightened awareness of the pathogen.

After this alert, the Colombian national health institute received an additional 78 C auris isolates from 24 healthcare facilities in nine states, for a total of 123 confirmed cases. Antifungal susceptibility testing on 93 of the isolates showed that 28 (30%) were resistant to fluconazole, 20 (22%) to amphotericin B, 1 (1%) to anidulafungin, and 1 (1%) to both amphotericin B and anidulafungin.

The authors conclude, "The number of reported cases likely does not reflect the true number of infected and colonized persons because of underreporting and underdiagnosis, as well as misdiagnosis as other yeast species."
Apr 20 MMWR report


New colistin resistance gene identified in Chinese poultry

Originally published by CIDRAP News Apr 18

Chinese scientists have discovered another colistin resistance gene in bacteria isolated from chickens, according to a study yesterday in the Journal of Antimicrobial Chemotherapy.

The plasmid-mediated gene was detected among 183 Klebsiella pneumoniae isolates collected from 2010 to 2015 from chickens in 13 Chinese provinces. Of the 10 colistin-resistant isolates detected, polymerase chain reaction (PCR) screening identified the MCR-1 gene in seven; the other three were negative for known colistin resistance genes. Whole-genome sequencing of one of the isolates identified a novel colistin resistance gene, dubbed MCR-7.1, in an Inc12-type plasmid that also harbored the blaCTX-M-55 beta-lactam resistance gene. Subsequent PCR screening showed that the other two K pneumoniae isolates also carried the MCR-7.1 gene. Conjugation experiments showed that the plasmid can successfully be transferred from K pneumoniae to E coli.

The researchers report that the amino acid sequence of MCR-7.1 shares a 70% similarity with MCR-3, and that the gene may have originated from Aeromonas species. They recommend screening bacteria in animals, humans, and the environment to understand dissemination of the gene throughout the world.

Before this discovery, various research groups had described MCR-1 though MCR-6 genes.
Apr 17 J Antimicrob Chemother abstract


Chinese study finds low MCR-1 prevalence in clinical isolates

Originally published by CIDRAP News Apr 18

In another study yesterday in the Journal of Antimicrobial Chemotherapy, a separate group of Chinese researchers report that the prevalence of MCR-1 among clinical isolates of E coli and K pneumoniae is low, but that MCR-1–positive E coli strains were highly resistant to other antibiotics.

The researchers from Peking University First Hospital and China Agricultural University analyzed 6,424 clinical E coli and K pneumoniae isolates collected from patients in Chinese hospitals from 2007 through 2016. Overall, 34 E coli isolates and 5 K pneumoniae isolates were positive for MCR-1. Multilocus sequence typing revealed high clonal diversity, identifying three different sequence types (STs) among the K pneumoniae isolates, and 28 distinct STs among the E coli isolates.

All the MCR-1–positive isolates were resistant to colistin, and MCR-1–positive E coli also displayed high levels of resistance to tetracycline, ciprofloxacin, and some cephalosporins. In addition, the researchers noted extremely significant difference in the rates of resistance to piperacillin, amikacin, nitrofurantoin, and fosfomycin between MCR-1–negative E coli and MCR-1–positive E coli. This finding, they suggest, indicates that infections caused by MCR-1–postive E coli strains should be treated differently than those caused by MCR-1–negative E coli.

All but six of the MCR-1–positive isolates (84.6%) were also extended-spectrum beta-lactamase producers, and 36 of the 39 (92.3%) were multidrug-resistant.
Apr 17 J Antimicrob Chemother abstract


High level of Shiga toxin-producing E coli found in Iranian dairy products

Originally published by CIDRAP News Apr 18

Iranian researchers report a high prevalence of Shiga toxin–producing E coli (STEC) with high levels of antibiotic resistance in raw milk and traditional dairy products.

In the study, published in Antimicrobial Resistance and Infection Control, the researchers collected 600 raw milk and traditional dairy product samples from producers in Isfahan province from March 2015 to March 2016, then cultured all the samples and isolated E coli strains. PCR was used to identify virulence factors, O-serogroups, and antibiotic resistance genes, and antibiotic resistance patterns were determined by disk diffusion.

Of the 600 samples tested, 181 (30.16%) were positive for E coli strains, with cheese (80%) and raw buffalo milk (50%) having the highest prevalence. Sixty-four of the E coli isolates were determined to be STEC strains, with O157 (43.75%) and O26 (37.5%) the most frequently identified serogroups.

Stx, eae, and ehly were the most commonly identified virulence factors in the STEC strains, and Aac(3)-IV, CITM, and tetA were the most commonly detected resistance genes. STEC strains harbored the highest prevalence of resistance against ampicillin (100%), gentamicin (100%), and tetracyclines (96.87%), and all of the STEC strains were resistant to at least one antibiotic. In addition, 43.75% were resistant to seven or more antibiotics.

The authors suggest that Iranian ranchers' use of their hands and traditional milking equipment could partially explain the high prevalence of E coli and STEC strains, as could keeping raw milk samples at temperatures that allow bacteria to proliferate and survive and using unpasteurized milk for production of dairy products. They also cite illegal and inaccurate use of antibiotics in veterinary medicine as the main reason for the high prevalence of antibiotic resistance in the STEC strains.
Apr 16 Antimicrob Resist Infect Control study


Paper describes One Health strategy for stewardship in South Africa

Originally published by CIDRAP News Apr 17

A commentary yesterday in The Lancet Infectious Diseases outlines the efforts by South Africa to promote stewardship of the last-resort antibiotic colistin, an approach the authors say is pertinent to all shared-use antibiotics.

In the paper, Marc Mendelson, PhD, and colleagues describe how South Africa has responded to the threat of losing colistin as a treatment for multidrug-resistant infections in humans through a One Health platform that promotes stewardship of the drug across human, animal, and environmental health. The response was prompted by the discovery of the mobile colistin-resistance gene MCR-1 in Escherichia coli in South African poultry and the identification of MCR-1-induced colistin resistance in South African patients.

The paper highlights the work of the Colistin Working Group, which was convened by the South African Medicines Control Council and first met in April 2016. Using data on colistin consumption and resistance levels in humans and animals in South Africa, along with a report on colistin from the European Medicines Agency, the group issued detailed recommendations on steps the South African government could take to mitigate colistin resistance. Among the recommendations was that colistin no longer be used in food-producing animals.

Since issuing that recommendations, the group has expanded to include additional stakeholders from various government departments and formed a One Health Stewardship Sub-Committee to take the work further.

"We believe that our approach of convening intersectoral stakeholders across the One Health platform to develop a national strategy for the stewardship of antibiotics provides valuable lessons for future work in South Africa, and that such a method could be useful in other countries," the authors write.
Apr 16 Lancet Infect Dis personal view


Algorithm helps identify antimicrobial peptide with therapeutic potential

Originally published by CIDRAP News Apr 16

An international team of scientists reports today on the use of a computational approach to develop an artificial antimicrobial peptide with the potential to treat gram-negative bacteria.

In a paper published in Nature Communications, researchers from the Massachusetts Institute of Technology (MIT) and the Catholic University of Brasilia describe their approach, which relies on a computer algorithm to generate and evaluate antimicrobial peptide sequences with the greatest potential for antimicrobial activity. Using as a template the plant peptide Pg-AMP1—which is found in the seeds of the guava plant but has only weak antimicrobial activity—the scientists generated 100 candidates and then synthesized them to test against bacteria grown in the lab.

The most promising of these candidates was guavinin 2, which was highly active against E coli and Acinetobacter baumannii, with limited activity against K pneumoniae and modest killing activity toward gram-positive bacteria. When tested in mice with a skin infection caused by Pseudomonas aeruginosa, guavanin 2 significantly reduced the bacterial count.

The scientists say they will continue developing guavanin 2 for use in humans and will use the algorithm to seek out other antimicrobial peptides.

"We can use computers to do a lot of the work for us, as a discovery tool of new antimicrobial peptide sequences," study co-author Cesar de la Fuente-Nunez, PhD, said in an MIT press release. "This computational approach is much more cost-effective and much more time-effective."
Apr 16 Nat Commun study 
Apr 16 MIT press release

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